It has proven difficult to recreate perceptually accurate and realistic touch and pressure sensation following thalamic stimulation in humans. Previous human experiments have used primarily single-site microstimulation with regular patterns of stimulation, which consistently results in a perception of tingling or paresthesias, and only occasionally a more natural sensation. We propose to perform multi-site microstimulation in human sensory thalamus during intra-operative experiments, while performing thalamic DBS surgery. During these experiments we will first test pairs of electrodes in a 16 or 32-channel Adtech microwire array and a Tucker- Davis acute, switching headstage. We have developed a switching unit to rapidly connect various pairs of electrodes for microstimulation. Using this switching unit connected to the headstage we can rapidly evaluate multiple pairs of electrodes for the evoked sensory response. These experiments are a natural extension of our large experience in recording with these microwire arrays from motor thalamus and subthalamic nucleus during a complex behavioral task (n = 52 patients). Then, we will next apply patterned microstimulation (10 - 50 5A) at dual or multiple microwire combinations in the sensory thalamus, to recreate the evoked actual mechanical skin input. Patterns will initially consist of a decelerating stimulus with an increasing interpulse interval (like an adapting primary sensory response), an accelerating stimulus with progressively shorter interpulse intervals, and a constant pulse sequence, with the same number of pulses applied over a 1 sec period. The patient's perception of the thalamic stimulation will then be critically assessed for these three patterns, while progressively altering the amplitude, the duration (from 100 to 1000 msec) and the location of the stimulation (to different pairs). These experiments will both help reveal the critical patterning of the natural evoked responses in sensory thalamus, as well as provide a potential substrate for insertion of realistic sensory inputs for development of a sensory prosthetic device. The R21 mechanism will be used to develop the programmed multisite microstimulation protocols and to assess the patient-derived concept of realistic perception, in direct comparison to a graded touch signal. Further tests will use a DBS macro-electrode, but with patterned microstimulation, to assess whether it is possible to extend the microwire data to a larger field. PUBLIC HEALTH RELEVANCE: This project will study how the brain processes sensation and the perception of sensation, in the human thalamus. This study will be important to understanding diseases where sensation is abnormally altered, such with nerve damage. This research may help to understand how an artificial sensory signal could be interpreted as a normal sensation, if the proper spatial and temporal pattern can be recreated. These results may lead to a sensory prosthesis to replace sensation where the nervous system has been damaged, for restoration of function.